Cold Exposure Rejuvenates the Metabolic Phenotype of Panx1−/− Mice

Pannexin1 (Panx1) ATP channels are important in adipocyte biology, potentially influencing energy storage and expenditure. The authors of this article compared the metabolic phenotype of young (14 weeks old) and mature (20 weeks old) wild-type (WT) and Panx1^−/− mice exposed or not to cold (6 °C) during 28 days, a condition promoting adipocyte browning. Young Panx1^−/− mice weighed less and exhibited increased fat mass, improved glucose tolerance, and lower insulin sensitivity than WT mice. Their energy expenditure and respiratory exchange ratio (RER) were increased, and their fatty acid oxidation decreased. These metabolic effects were no longer observed in mature Panx1^−/− mice. The exposure of mature mice to cold exacerbated their younger metabolic phenotype. The white adipose tissue (WAT) of cold-exposed Panx1^−/− mice contained more small-sized adipocytes, but, in contrast to WT mice, white adipocytes did not increase their expression of Ucp1 nor of other markers of browning adipocytes. Interestingly, Glut4 expression was already enhanced in the WAT of young Panx1^−/− mice kept at 22 °C as compared to WT mice. Thus, Panx1 deletion exerts overall beneficial metabolic effects in mice that are pre-adapted to chronic cold exposure. Panx1^−/− mice show morphological characteristics of WAT browning, which are exacerbated upon cold exposure, an effect that appears to be associated with Ucp1-independent thermogenesis.

Full article: https://doi.org/10.3390/biom14091058

This research was supported by a grant from the Swiss National Science Foundation.

WHY IS IT IMPORTANT?

This study investigated the role of pannexin1 (Panx1) channels in energy metabolism, fat storage and cold-induced adipocyte changes (browning) in mice. Young Panx1-deficient mice had greater fat mass and better glucose control than wild-type mice. When exposed to cold, Panx1-deficient mice showed signs of adipocyte browning, but unlike typical brown fat, the expression of Ucp1, a protein known to be key to thermogenesis, was not increased. These findings suggest that Panx1 plays a complex role in the regulation of adipose tissue and energy metabolism, particularly under cold conditions.

In this article, the authors suggest new ways of understanding metabolic regulation, energy balance and ageing. This could have important implications for obesity and diabetes research.

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